Various tumor related diseases inflict man. Considerable research has been devoted to oncology and antitumor measures. Tumors are common in a variety of mammals and the prevention, control of the growth and regression of tumors in mammals is important to man. Malignant tumors inflict mammals and man with a variety of disorders and conditions including various forms of cancer and leukemia. The seriousness of cancer is well known, e.g., cancer is second only to heart and vascular diseases as a cause of death in man.
Several naturally-occuring alkaloids have been found active in the treatment of experimental malignancies in animals. Among these are vinblastine and vincristine which are now marketed as drugs for the treatment of malignancies, particularly the leukemias and related diseases in humans.
Isolation of vinblastine from the Catharanthus roseus plant is disclosed, for example, by the following patents:
U.S. Pat. No. 3,205,220 to Svoboda et al. discloses a process for extracting vinblastine utilizing hexane to initially defat the roseus plants and extraction of vinblastine from the plant with 2% tartaric acid and portions of benzene.
U.S. Pat. No. 4,203,898 to Cullinan et al. discloses utilizing benzene as a water immiscible solvent for extracting vinca alkaloids from the Catharanthus roseus plant, the benzene solvent is combined with an aqueous acidic extract which is then adjusted to a pH of 6 or 7. An optional gel exclusion filtration step is disclosed utilizing a c:oss-linked dextran gel (Sehadex G-25F) in a citrate buffer system.
U.S. Pat. No. 3,932,417 to Jones discloses a method for preparing vinca alkaloids utilizing an aqueous acid solution and benzene as preferred extracting solvents and also discloses that other water immiscible solvents may be used in place of benzene (e.g. toluene). Jones utilizes a citrate buffer as part of the optional gel exclusion purification step.
U.S. Pat. No. 4,172,077 to Jovanics et al. broadly discloses extraction of vinca alkaloids from roseus plants with various solvents including a mixture of a lower alkanol and dilute aqueous acid and purification of the alkaloids by phase-change methods.
While these references disclose various methods for isolating vinca alkaloids further methods which may involve simpler procedures and/or higher yields are desirable.